Back to resultsCombination Study of IPH2201 (Monalizumab) With Ibrutinib in Relapsed, Refractory or Previously Untreated CLL
Primary Purpose
Chronic Lymphocytic Leukemia
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
monalizumab
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Lymphocytic Leukemia
Eligibility Criteria
Inclusion Criteria:
- Confirmed diagnosis of Chronic Lymphocytic Leukemia (CLL)
- Relapsed, refractory or previously untreated CLL
- CLL requiring treatment; patients must be eligible for ibrutinib therapy
- Age > = 18 years
- Eastern Cooperative Oncology Group performance status of 0-2
- Life expectancy > = 3 months
- Adequate liver and renal function
- Negative serum pregnancy test within 72 hours before starting study treatment in women with childbearing potential. Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of the study participation
- Ability to understand a written informed and consent document
- Signed informed consent prior to any protocol-specific procedures
Exclusion Criteria:
- Patients who have previously received ibrutinib or another inhibitor of Bruton's tyrosine kinase (BTK)
- History of allergic reactions attributed to compounds or similar chemical or biological composition to ibrutinib
- Central nervous system involvement of the CLL
- Abnormal hematological function which is not due to bone marrow failure related to the CLL
- Patients requiring a treatment by oral vitamin K antagonists
- Serious uncontrolled medical disorder
- Medical condition or organ system dysfunction which, in the investigator opinion, could interfere with absorption or metabolism of ibrutinib
- Moderate or severe hepatic impairment
- Active auto-immune disease
- Abnormal cardiac status
- Pregnant women are excluded from study
- Current active infectious disease
- History of another malignancy within 3 years
- History of allogeneic stem cell or solid organ transplantation
Sites / Locations
- The Ohio State University Wexner Medical Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Phase 1 Level 1 - 1 mg/kg
Phase 1 Level 2 - 2 mg/kg
Phase 1 Level 3 - 4 mg/kg
Phase 2 RP2D - 2 mg/kg
Arm Description
In phase 1, Monalizumab given at the first dose level of 1 mg/kg.
In phase 1, Monalizumab given at the second dose level of 2 mg/kg.
In phase 1, Monalizumab given at the third dose level of 4 mg/kg.
In phase 2, Monalizumab given at the Recommended Phase 2 Dose (RP2D) of 2 mg/kg, selected by a safety committee.
Outcomes
Primary Outcome Measures
Number of Dose Limiting Toxicities
Number of dose-limiting toxicities, measured during the phase 1, dose escalation, part of the study.
Rate of Complete Response (CR)
The rate of complete response (CR) was evaluated using the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) grading scale and confirmed by a bone marrow biopsy. Per International Workshop on Chronic Lymphocytic Leukemia (IWCLL), Complete Response (CR) is defined as lymphocytes <4x109/l, absence of lymphadenopathy, hepatomegaly and splenomegaly at CT scan, no constitutional symptoms, no cytopenia, normocellular bone marrow. Partial Response (PR) is a reduction > 50% in lymphocytes, lymphadenopathy, spleen or liver, no cytopenia. PD if appearance of any new lesion, or increase in lymphocytes > 50%, or occurrence of cytopenia attributable to CLL.
Secondary Outcome Measures
Best Overall Response / Remission Rates
Measure of best overall response at any time during the study. cCR: confirmed complete response/remission; uCR: unconfirmed complete response / remission; PR: partial response/remission; SD: stable disease; PD: progressive disease.
Per International Workshop on Chronic Lymphocytic Leukemia (IWCLL), Complete Response (CR) is defined as lymphocytes <4x109/l, absence of lymphadenopathy, hepatomegaly and splenomegaly at CT scan, no constitutional symptoms, no cytopenia, normocellular bone marrow. Partial Response (PR) is a reduction > 50% in lymphocytes, lymphadenopathy, spleen or liver, no cytopenia. PD if appearance of any new lesion, or increase in lymphocytes > 50%, or occurrence of cytopenia attributable to CLL.
In order to have a confirmed CR (cCR), the CR must be confirmed by a scan and a bone marrow assessment assessed at least 2 months after the first occurrence of CR. Otherwise it would be an unconfirmed CR (uCR).
Duration of Remission
The duration of remission (DOR) is defined as the time from the date of first evaluation of the remission (cCR, uCR or PR) to the first documentation of progressive disease, relapsed disease or death. In case an assessment of progressive / relapsed disease or death does not exist, the DOR was censored at the time of the last disease assessment date. The DOR was calculated only for the patients with a remission that was assessed at 52 weeks.
Progression Free Survival
The Progression Free Survival (PFS) is defined as the time from first dose administration until the occurrence of progressive disease, relapsed disease or death from any cause. Patients without an event at the time of the analyse were censored at his or her last disease assessment date. Patients with no post-Baseline assessment were censored at the day of the first dose administration.
Overall Survival
The overall survival (OS) is defined as the time from first dose administration until death from any cause. Alive patients were censored at the most recent date they were known to be alive. Subjects with no assessment post-Baseline were censored at the day of the first dose administration.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02557516
Brief Title
Combination Study of IPH2201 (Monalizumab) With Ibrutinib in Relapsed, Refractory or Previously Untreated CLL
Official Title
Open Label 1b/2a Trial of a Combination of IPH2201 and Ibrutinib in Patients With Relapsed, Refractory or Previously Untreated Chronic Lymphocytic Leukemia
Study Type
Interventional
2. Study Status
Record Verification Date
December 2019
Overall Recruitment Status
Terminated
Why Stopped
Sponsor decision
Study Start Date
November 9, 2015 (Actual)
Primary Completion Date
October 29, 2018 (Actual)
Study Completion Date
September 25, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Innate Pharma
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Combination study of monalizumab (IPH2201) with Ibrutinib in relapsed, refractory or previously untreated Chronic Lymphocytic Leukemia (CLL) patients in 2 parts :
phase 1 : a 3+3 design to assess the Maximum Tolerated Dose (MTD)
phase 2: to evaluate the anti-leukemic activity of the combination
Detailed Description
This trial was designated to test the hypothesis that the combination of ibrutinib and IPH2201 will result in a substantial complete response (CR) rate, especially CR without minimal residual disease (MRD), as this has been shown to be associated with long-term clinical benefit.
Up to 45 patients were planned to be enrolled. During the phase 1 part a 3+3 dose escalation design was employed. Four doses were planned to be assessed if the Maximum Tolerated Dose (MTD) was not previously reached: 1, 2, 4 and 10 mg/kg.
During phase 2 part, patients received monalizumab in combination with ibrutinib; monalizumab was given at the dose recommended upon completion of the phase I portion.
The primary objective of the phase 1 was to assess the safety of monalizumab given intravenously as a single agent and in combination with ibrutinib in patients with relapsed, refractory or previously untreated Chronic Lymphocytic Leukemia.
The primary objective of the phase 2 was to evaluate the anti-leukemic activity of the combination of monalizumab and ibrutinib in patients with relapsed, refractory or previously untreated Chronic Lymphocytic Leukemia.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Lymphocytic Leukemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
22 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Phase 1 Level 1 - 1 mg/kg
Arm Type
Experimental
Arm Description
In phase 1, Monalizumab given at the first dose level of 1 mg/kg.
Arm Title
Phase 1 Level 2 - 2 mg/kg
Arm Type
Experimental
Arm Description
In phase 1, Monalizumab given at the second dose level of 2 mg/kg.
Arm Title
Phase 1 Level 3 - 4 mg/kg
Arm Type
Experimental
Arm Description
In phase 1, Monalizumab given at the third dose level of 4 mg/kg.
Arm Title
Phase 2 RP2D - 2 mg/kg
Arm Type
Experimental
Arm Description
In phase 2, Monalizumab given at the Recommended Phase 2 Dose (RP2D) of 2 mg/kg, selected by a safety committee.
Intervention Type
Drug
Intervention Name(s)
monalizumab
Other Intervention Name(s)
Anti-NKG2A, IPH2201
Intervention Description
During phase 1, patients received monalizumab, IV, at the dose of 1, 2 or 4mg/kg, as a single agent during 4 weeks and thereafter combined with ibrutinib 420 mg, orally, once daily, during 52 weeks.
During phase 2, patients received monalizumab, IV, at the dose recommended upon completion of phase 1, combined with ibrutinib 420 mg orally, once daily, from the first cycle, during 52 weeks. In both parts of the trial, the first 4 administrations of monalizumab (from week 0 to week 6) occured every 2 weeks. From the 5th administration monalizumab was administered every 4 weeks.
Primary Outcome Measure Information:
Title
Number of Dose Limiting Toxicities
Description
Number of dose-limiting toxicities, measured during the phase 1, dose escalation, part of the study.
Time Frame
8 weeks
Title
Rate of Complete Response (CR)
Description
The rate of complete response (CR) was evaluated using the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) grading scale and confirmed by a bone marrow biopsy. Per International Workshop on Chronic Lymphocytic Leukemia (IWCLL), Complete Response (CR) is defined as lymphocytes <4x109/l, absence of lymphadenopathy, hepatomegaly and splenomegaly at CT scan, no constitutional symptoms, no cytopenia, normocellular bone marrow. Partial Response (PR) is a reduction > 50% in lymphocytes, lymphadenopathy, spleen or liver, no cytopenia. PD if appearance of any new lesion, or increase in lymphocytes > 50%, or occurrence of cytopenia attributable to CLL.
Time Frame
CR assessed 52 weeks after the beginning of combination treatment
Secondary Outcome Measure Information:
Title
Best Overall Response / Remission Rates
Description
Measure of best overall response at any time during the study. cCR: confirmed complete response/remission; uCR: unconfirmed complete response / remission; PR: partial response/remission; SD: stable disease; PD: progressive disease.
Per International Workshop on Chronic Lymphocytic Leukemia (IWCLL), Complete Response (CR) is defined as lymphocytes <4x109/l, absence of lymphadenopathy, hepatomegaly and splenomegaly at CT scan, no constitutional symptoms, no cytopenia, normocellular bone marrow. Partial Response (PR) is a reduction > 50% in lymphocytes, lymphadenopathy, spleen or liver, no cytopenia. PD if appearance of any new lesion, or increase in lymphocytes > 50%, or occurrence of cytopenia attributable to CLL.
In order to have a confirmed CR (cCR), the CR must be confirmed by a scan and a bone marrow assessment assessed at least 2 months after the first occurrence of CR. Otherwise it would be an unconfirmed CR (uCR).
Time Frame
From beginning of study drug treatment to the end of study (up to 24 months)
Title
Duration of Remission
Description
The duration of remission (DOR) is defined as the time from the date of first evaluation of the remission (cCR, uCR or PR) to the first documentation of progressive disease, relapsed disease or death. In case an assessment of progressive / relapsed disease or death does not exist, the DOR was censored at the time of the last disease assessment date. The DOR was calculated only for the patients with a remission that was assessed at 52 weeks.
Time Frame
Up to 24 months
Title
Progression Free Survival
Description
The Progression Free Survival (PFS) is defined as the time from first dose administration until the occurrence of progressive disease, relapsed disease or death from any cause. Patients without an event at the time of the analyse were censored at his or her last disease assessment date. Patients with no post-Baseline assessment were censored at the day of the first dose administration.
Time Frame
Up to 24 months
Title
Overall Survival
Description
The overall survival (OS) is defined as the time from first dose administration until death from any cause. Alive patients were censored at the most recent date they were known to be alive. Subjects with no assessment post-Baseline were censored at the day of the first dose administration.
Time Frame
Up to 24 months.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Confirmed diagnosis of Chronic Lymphocytic Leukemia (CLL)
Relapsed, refractory or previously untreated CLL
CLL requiring treatment; patients must be eligible for ibrutinib therapy
Age > = 18 years
Eastern Cooperative Oncology Group performance status of 0-2
Life expectancy > = 3 months
Adequate liver and renal function
Negative serum pregnancy test within 72 hours before starting study treatment in women with childbearing potential. Women of child-bearing potential and men must agree to use adequate contraception prior to study entry and for the duration of the study participation
Ability to understand a written informed and consent document
Signed informed consent prior to any protocol-specific procedures
Exclusion Criteria:
Patients who have previously received ibrutinib or another inhibitor of Bruton's tyrosine kinase (BTK)
History of allergic reactions attributed to compounds or similar chemical or biological composition to ibrutinib
Central nervous system involvement of the CLL
Abnormal hematological function which is not due to bone marrow failure related to the CLL
Patients requiring a treatment by oral vitamin K antagonists
Serious uncontrolled medical disorder
Medical condition or organ system dysfunction which, in the investigator opinion, could interfere with absorption or metabolism of ibrutinib
Moderate or severe hepatic impairment
Active auto-immune disease
Abnormal cardiac status
Pregnant women are excluded from study
Current active infectious disease
History of another malignancy within 3 years
History of allogeneic stem cell or solid organ transplantation
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kerry A Rogers, MD
Organizational Affiliation
Ohio State University
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Ohio State University Wexner Medical Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Combination Study of IPH2201 (Monalizumab) With Ibrutinib in Relapsed, Refractory or Previously Untreated CLL
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